Statins (HMG-CoA reductase inhibitors) are drugs of choice for lipid lowering in patients at increased risk for cardiovascular disease (CVD) and for those with established atherosclerotic VD (secondary prevention). CV risk using risk calculators should be assessed prior to initiation of a statin for most patients being treated for primary prevention of atherosclerotic CVD. Guidelines vary regarding threshold for using statins for primary prevention: the American College of Cardiology/American Heart Association recommends statin therapy for patients in the following groups: patients with a 10-year risk of CVD >/=7.5% with consideration at risk 5% to 7.5%; patients with low-density lipoprotein (LDL) cholesterol >/=190 mg/dL; patients aged 40-75 years with diabetes (type 1 or 2) and LDL cholesterol >/=70 mg/dL. The National Institute for Health and Care Excellence recommends statin therapy if 10-year risk of CVD >/=10%. The European Society of Cardiology/European Atherosclerosis Society recommends statin therapy if estimated 10-year risk of first fatal atherosclerotic event >/=10%. Use of statin in intermediate-risk population also resulted in a significantly lower risk of CV events. Statins are well tolerated, but various statin-associated symptoms (SAS) might occur, including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These SAS are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving drugs. SAMS is the most frequent SAS, and mild myalgia may affect 5-10% of statin users. Clinically important muscle symptoms are rare, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM). Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is not clear. The highest risk for incident diabetes with statins was found in older patients, independently of BMI at inclusion and changes in LDL cholesterol. The preventive effect on cardiovascular events did not change according to changes in HbA1c levels. These observations do not justify any change in clinical practice, except perhaps for a closer follow-up of HbA1c levels after initiating statin therapy. Management of SAS requires making the diagnosis, changing or adjusting the statin treatment, and using alternative lipid-lowering therapy.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Stroke is one of the major causes of death and morbidity worldwide and carries an important economic impact. The diagnosis is still a clinical one, supported by brain imaging. However, up to 30% of suspected stroke presentations, have a different diagnosis. In these cases, two scenarios must be considered: a false positive diagnosis, or “stroke mimic”, and a false negative or “stroke chameleon”.
Although a sudden onset of a neurological deficit usually represents a stroke, other conditions such as seizures (especially if Todd´s palsy is present), syncope, hypoglycaemia, migraine, brain tumours and functional disorders represent the bulk of the differential diagnosis. The accuracy of their recognition depends on context (primary care vs paramedics vs emergency department vs stroke specialist). Even the stroke specialists may have up to 15% of misdiagnoses. Brain imaging is a powerful helper. Non-contrast CT scanning has become the primary imaging modality in the initial assessment, mainly due to its wide availability, rapid execution and lack of major contraindications (such as pacemaker). It detects fairly easily an acute haemorrhagic stroke or a non-vascular structural cause of stroke mimic (such as a space-occupying lesion). However, the majority of strokes are ischaemic, and the initial CT-scan may be negative. Brain MRI, on the other hand, and in particular diffusion weighted imaging (DWI), have 88-100% sensitivity and 95-100% specificity for early ischaemia. A variety of other neurological conditions may be DWI positive, and so, clinical context must be considered. DWI negatives are rare, mainly associated with small lesions in the brainstem, and, as described more recently, are overcome by associating perfusion-weighted imaging. Nevertheless, MRI is time consuming and may not be immediately available, and therefore most clinicians still administer thrombolytic therapy base on clinical evaluation and non-contrast CT-scan. Inadvertently but inevitably, stroke mimics also receive this treatment. Although inadequate, it is relatively safe, with a low likelihood of complications (<1%).
Stroke can have an unusual presentation and can often not be immediately recognized. Although rare, vertigo may be a manifestation of stroke. A thorough neurological examination, particularly focusing on the head impulse test, evaluation of nystagmus and skew deviation, can properly distinguish a peripheral lesion from a vertebrobasiIar stroke. Other findings, such as monoplegia or delirium, may infrequently be the sole manifestation of stroke.
In conclusion, the identification of stroke can be difficult. The full workup (including MRI) of all patients that may have a stroke is probably not feasible, and an initial clinical evaluation is still an important screening tool. In the future, the development of blood biomarkers of cerebral ischaemia may further help the accurate detection of this common diagnosis.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Headache and stroke are both fairly prevalent conditions, and their association could be deemed coincidental. However, the interaction of these conditions is far more complex. Headache may either be a cause or consequence of stroke and, then again, headache syndromes can mimic stroke and vice versa. Discussion of these issues is further complicated by the diversity of headache and stroke sub-types.
Overall, up to 34% of stroke patients present with headache. While the brain is largely devoid of sensation, mechanical insults or inflammation of other cranial structures (the dura and dural sinuses, skull base and meningeal arteries and selected cranial nerves) are likely to elicit pain.
Thus, it can easily be understood why headache is classically associated with haemorrhagic stroke. In fact, severity of headache has been studied as a prognostic factor in symptomatic intracerebral haemorrhage. Furthermore, subarachnoid haemorrhage, clinically characterized by thunderclap headache, has the highest association with headache (>90% of cases).
On the other hand, ischaemic stroke (IS) presents with headache less frequently (up to 25% of cases). The headache is usually non-pulsatile and ipsilateral to the lesion. The likelihood of headache is higher when the infarct is large and when it affects the insular cortex or the posterior circulation. The likelihood is lower in lacunar syndromes. In the setting of IS, headache may point the clinician to an arterial dissection or to a migrainous infarction, among others. The latter is said to occur in a patient with typical aura lasting more than one hour and neuroimaging-confirmed ischaemia.
Other cerebrovascular disorders such as cerebral venous thrombosis, reversible vasoconstriction syndrome, posterior reversible encephalopathy syndrome and vasculitides also present with headache and will be briefly mentioned.
In conclusion, headache is a non-specific, albeit clinically useful, sign in acute stroke. Thus, this complex relationship should be kept in mind when considering the differential diagnosis of acute neurological deficits.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Recently, multiple randomized controlled trials demonstrated a high degree of efficacy for endovascular treatment with stent-retriever in strokes caused by large-vessel occlusions. In these trials, the benefit of endovascular therapy was directly related to baseline imaging markers, such as identification of a large artery occlusion, existence of a small infarct core, documentation of adequate collateral circulation and estimation of a target mismatch.
In this new era of acute stroke therapy, controversy persists about the optimal approach to patient selection based on brain imaging. The reduction of the time from onset of symptoms to reperfusion is crucial for a favourable long-term outcome in stroke patients – “time is brain” – therefore we need an imaging strategy to avoid any important delay.
A CT-based imaging approach is the mainstay of acute stroke imaging. Several studies demonstrated the same quality of MRI when compared to a combination of non–contrast-enhanced CT (exclusion of intracranial haemorrhage and measure of early ischemic changes), CT Angiography (identifying the target thrombus) and CT Perfusion Imaging (tissue at risk), in detecting and quantifying signs of cerebral ischemia due to large artery occlusion. Nevertheless, MRI is more sensitive than CT in detecting small lesions and/or posterior fossa ischaemic lesions.
In our practice, we are focused on minimizing delays to reperfusion, providing fast imaging paradigms with the essential information necessary for decision-making. The combination of the clinical assessment, non–contrast-enhanced CT and CT Angiography, supports the selection of suitable patients for endovascular revascularization. We are moving from a rigid time-based to a physiology-based decision, selecting patients for treatment beyond the 6-hour window if there is evidence of a significant imaging/clinical mismatch.
Imaging has, therefore, a key role in medical and endovascular treatment decisions, overtaking time as the single surrogate marker of brain physiology.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Intravenous fibrinolytic therapy has been used for acute ischemic stroke with wide acceptance for more than 15 years. The aim of this presentation is to review the literature, clinical protocols and some common dilemmas regarding pharmacological revascularization in acute ischemic stroke. The story starts with the NINDS trial (1996) which supported the efficacy of recombinant tissue plasminogen activator (rtPA) not only in early neurological recovery but also in better functional outcome at 3 months. The protocol included the use of 0.9 mg/kg intravenous rTPA to a maximum of 90 mg within 3 hours of symptom onset. Afterwards, the ECASS III trial (2008) stretched the time window to 4.5 hours. The major risk of intravenous rtPA treatment remains symptomatic intracranial haemorrhage which occurs in 2-6% of patients. The SITS-ISTR (Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Register), the largest community registry, reported that in 11 865 patients treated with rTPA, 56% of them were independent at 3 months. The last chapter in the rTPA saga was the meta-analysis published in 2012, which depicts the safety of rTPA across all age groups. Common dilemmas in clinical practice are patients presenting with minor or fluctuating deficits, on oral anticoagulants and other items of an extensive and cumbersome contra-indication list. Other pharmacological agents and Transcranial Ultrasound Fibrinolysis Augmentation will be shortly reviewed. In conclusion, timely given rtPA remains the primary treatment in acute ischemic stroke, but recent advances in mechanical revascularization may challenge this mainstream paradigm. The epilogue remains, thus far, unwritten.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

The year of 2015 was a hallmark for the treatment of acute stroke. The publication of the MR CLEAN trial elicited a cascade of positive results from six additional stroke randomized controlled trials: ESCAPE, EXTEND-IA, REVASCAT, SWIFT PRIME, THERAPY and THRACE, which were halted prematurely for efficacy. The cumulative evidence from these studies shows an overwhelming benefit from the endovascular treatment of intracranial large artery occlusions. The published trials led to guideline changes in the USA and Europe, which reflect the major common factors amongst studies, but the need for clinical judgment remains significant, especially in patients who do not neatly fit the patient population enrolled in the trials, but who probably also benefit from this treatment. All studies (with the exception of THERAPY) involved new generation devices, namely stent retrievers. Although most of the technical approaches, with some variations, are relativity standardized, many uncertainties remain for specific situations such as tandem occlusions or intracranial stenosis. The decision to use general anaesthesia or conscious sedation has also been the topic of much debate. Early studies showed worse outcomes associated with general anaesthesia but were confounded by indication, that is, medically unwell patients with poorer prognosis were more likely to undergo general anaesthesia. The MR CLEAN trial addressed this issue, and treatment effect was clearly greater in those treated under conscious sedation. The concern regarding thrombectomy costs has also been addressed. The studies concluded that, although the upfront costs of thrombectomy are high, the potential quality-adjusted life year gains mean this intervention is cost-effective.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Identifying the stroke mechanism is a crucial aspect of secondary prevention. However, no stroke etiology is identified in 30-40% of patients. Cryptogenic stroke is the term used to refer to strokes for which no definite cause can be identified.
Thrombophilia is defined as a predisposition to form clots inappropriately, and can be inherited or acquired. The inherited thrombophilias include deficiency of natural anticoagulants, such as protein C, protein S or antithrombin, and factor V Leiden or prothrombin G20210A gene mutation. The most important acquired thrombophilias are antiphospholipid syndrome and cancer.
Thrombophilia is an important risk factor for venous thromboembolism, but its role in arterial thrombosis is not well defined. The presence of thrombophilia has been accurately investigated in this setting, obtaining controversial results. Multiple case-control studies and a meta-analysis failed to show an association between inherited thrombophilia and stroke. The only strong association found was with the presence of antiphospholipid antibodies, both in retrospective and prospective studies. Plasma levels of antiphospholipid antibodies were elevated in young adults who suffered a stroke compared with controls, and these patients presented a higher risk of recurrent thrombotic events.
Before performing these tests, all other causes must be ruled out. There are many doubts if the information obtained in thrombophilia screening is sufficiently relevant to change clinical decision, regarding secondary prevention. As a consequence, there is no consensus about the clinical utility and cost effectiveness of thrombophilia screening in arterial thrombosis.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Recent data show that stroke is one of the main causes of death and the main cause of neurological disability in the adult. It is also a major cause of dementia and age related cognitive decline. Conventional cardiovascular risk factors explain a significant percentage of stroke risk, but an important part of that risk remains without explanation. Additionally, different individuals have different outcomes when exposed to the same risk factor. This means that genetic factors have an important role in stroke risk determination. Unlike other cardiovascular diseases, stroke is a heterogeneous disorder and genetic factors can affect stroke pathophysiology at different levels. Taking this into consideration, we can identify several inherited metabolic disorders, usually with multisystemic presentations, that can have stroke as one of their phenotypic expressions. We have disorders that express themselves as small- or large-vessel disease patterns, as cardioembolic causes or other kind of profiles (for instance, stroke-like in MELAS). This group of disorders, although individually rare, are collectively frequent and they can appear at any age, from the newborn to the elderly. Due to their rarity, they are frequently not recognized or taken into account in diagnostic flowcharts, although for a significant number of them we have specific treatments that can improve prognosis significantly.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

The incidence of ischaemic stroke and transient ischaemic attack (TIA) in young adults is increasing, and this implies a great early death risk compared with the general population. A wide range of different etiologies is found in this group, and a careful anamnesis, physical examination and workup is essential for its diagnosis and proper management. Standard risk factors are still prevalent in this age group, and they should be considered in the initial evaluation. Special emphasis should be given to cervical artery dissection, right-to-left shunts and hypercoagulable states in young stroke patients. A wide variety of rarer causes should also be considered when the remainder of the workup is negative.
In this protocol, we propose a methodical diagnostic approach to TIA and ischaemic stroke in young adults.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Ischaemic strokes are attributed to a cardioembolic cause in approximately 20% of cases and atrial fibrillation (AF) is the most common cardioembolic source. AF is also associated with larger, more disabling and higher case fatality strokes which highlights the major importance of primary prevention with oral anticoagulants (OAC). Identifying patients with AF and other cardiovascular risk factors for starting these drugs is as important as evaluating their bleeding risk. CHA2DS2-VASc and HAS-BLED are two important tools, with the first helping deciding who to anticoagulate and the second serving as a guide to reduce modifiable bleeding risks (not to determine whether to offer anticoagulation or not).
If starting anticoagulation is becoming more common for primary prevention, the resumption of this therapy after ischaemic and haemorrhagic stroke is sometimes delayed or avoided. However, several studies have already shown that resumption is important to decrease stroke recurrence and all-cause mortality, outweighing the major concern - intracranial bleeding. Resuming OAC may be contraindicated in some cases, for example when a lobar haematoma is associated with cerebral amyloid angiopathy.
Still, the most difficult decision is not usually whether or not to start anticoagulation, but the ideal timing to do it. There are not enough data about this topic, although many observational studies have shown positive results with starting OAC between 36h to 90 days after the event.
In clinical practice, the timing often depends on the indication for anticoagulation and on the thrombotic risk associated with the disease. Decision must also take in consideration the size of the ischaemic lesion, the location and dimension of the intracranial hematoma and the adequate control of hypertension, which are the main risk factors for (re)bleeding.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Upon the diagnosis of an embolic stroke, the absence of significant arterial pathology in the symptomatic vessels, major cardiac sources of emboli and “other specific causes of stroke” will allow the formal classification of an embolic stroke of undetermined source (ESUS). And what is there to do then?
Firstly, we should critically review the diagnostic work-up performed. Were all causes of embolic stroke really excluded? Regarding arterial pathology, occasionally the source of embolus is in less frequent locations that should be kept in mind. Complex atherosclerotic plaques in the aortic arch, distal extracranial or proximal intracranial vessels are locations often neglected. Moreover, attention should be paid to arterial pathology without hemodynamic impact, such as some cases of dissection or vasculitis, that may be overlooked, requiring specific exams. A routine ECG and 24-hour ECG monitoring excluding the presence of a potentially embolic arrhythmia may be enough for the formal classification of ESUS. However, they should not reassure the attending physician. Longer cardiac monitoring through implantable and non-implantable devices has been demonstrated to improved diagnostic labelling.
The remaining critical question is what thromboprophylaxis strategy to use. Considering the medical equipoise at this time point of knowledge, the logical answer, whenever possible, can be only one: randomize! In case no trial is available for a specific patient, the decision should, like always, be shared by physician and patient after careful consideration.
In sum, ESUS patients require a specific diagnostic and therapeutic approach that will surely be progressively reconsidered during the following years.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Cognitive dysfunction of vascular origin may be defined as any type of cognitive or behavioural impairment that results from nervous system damage and neuronal loss caused by cerebrovascular disease. It may be slowly progressive, in relation with vascular risk factor exposure, or of sudden onset after stroke or even transient ischaemic attack. At least one third of stroke patients show cognitive impairment 3 months after the acute phase, with the most affected domains being attention, executive functioning and processing speed. These deficits contribute to overall functional impairment and may even lead to dementia, but they also interfere significantly with rehabilitation programs.
However, there are very limited pharmacological treatment approaches for the management of cognitive impairment after stroke. Therefore, cognitive interventions are an increasingly common approach in stroke rehabilitation programs, either isolated or combined. If we consider the non-motor aspects of the human brain, cognitive training must be understood in a similar manner as physical therapy for motor deficits. Despite the continuum between cognitive, behavioural and motor functions, the former are more complex and supported on memory and other distributed neural systems, which presents specific challenges for the design of effective interventions. These may be defined as a group of non-pharmacological interventions, specifically conceived with the purpose of improving cognitive and behavioural performance in stroke patients.
During this lecture, we will review the indications, methods and recent scientific evidence on the effects of specific neuropsychological interventions in cognitive dysfunction of vascular origin and after stroke.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Spontaneous, non-traumatic intracerebral haemorrhage (ICH) remains a significant cause of morbidity and mortality, as it is the second most common cause of stroke. High blood pressure and age are the most important risk factors. However, the investigation should include a search for other causes including use of anticoagulants or antiplatelet agents, coagulopathy and other comorbidities such as dementia, epilepsy, cancer or hepatic disease.
The CT scan remains the gold standard for diagnosis in emergency care. On the other hand, brain magnetic resonance angiography should be performed in the case of single/multiple lobar haemorrhages. These can be secondary to amyloid angiopathy, rupture of an aneurism or an arteriovenous malformation, cavernous angioma or tumour haemorrhage.
Radiological evidence suggestive of vascular abnormalities as causative for ICH can include the presence of subarachnoid haemorrhage, enlarged vessels or calcifications along the margins of the ICH, hyperattenuation within a dural venous sinus or cortical vein along the presumed venous drainage path, unusual hematoma shape, presence of oedema out of proportion to the time of presumed installation, an unusual location, and the presence of other abnormal structures in the brain (such as a mass). Magnetic resonance venography and catheter angiography can be performed in specific situations.

Special Issue on Stroke Updates. From Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–9 June 2016.

Intracerebral haemorrhage (ICH) accounts for 10-25% of all strokes, and despite its incidence, associated disability and mortality have been decreasing in high-income countries. Nevertheless, it is associated with a high one-month mortality, which may reach up to 40%. Medical management of ICH patients in the hyperacute and acute phases is a challenge, which requires continuous monitoring and up to date therapeutic interventions, even in patients who need surgical treatment. The ABCD approach is discussed as a guideline for a systematic and quick evaluation of ICH patients in the emergency department, as it is able to address priority concerns in these patients, namely airway management and indication for tracheal intubation, blood pressure management, neurological evaluation and reversal of antithrombotic medication. Patients with ICH should be preferentially admitted in acute stroke units or dedicated neurocritical care units, which have shown to improve mortality and disability. General management of practical issues such as timing of out-of-bed mobilization, timing of nutrition, measures for prevention of infections, deep vein thrombosis prophylaxis and epileptic seizure prevention are also discussed.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

When to treat? The answer to this question depends on the diagnosis and clinical presentation, which may be with or without rupture. Vascular lesions [aneurysms or arteriovenous malformations (AVM)] with haemorrhage should be treated as soon as possible, and this is particularly true when dealing with aneurysms. In the last years, there has been a change in the paradigm of timing to treat aneurysms with sub-arachnoid haemorrhage (SAH). Initially, treatment was postponed until after the risk period for vasospasm has passed. Later on, the patients started being treated earlier (in the first 72 hours after the SAH). Nowadays, there is a tendency for even earlier treatment (less than 24 hours after SAH).
How to treat? Concerning aneurysms, there are two treatment modalities: surgery or endovascular treatment. As for AVMs, apart from the options of surgery and endovascular treatment, there is also the option of radiosurgery. In this case, treatment can be complementary, with two or three modalities possibly being used in the same patient. In aneurysms, the treatment modality depends on their location, morphology, vascular tree features, age and neurological status. In cases where both surgery and embolization are feasible, embolization should be chosen, as it is the least invasive. Even though initially all patients underwent surgery, endovascular treatment has evolved and has progressively expanded its indications. Nowadays, treatment decisions are the result of a multidisciplinary discussion between Neurosurgery and Neuroradiology, balancing the best immediate care with long term results.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

The National Institutes of Health Stroke Scale (NIHSS) is an assessment tool used worldwide to quantify neurological deficit in people with stroke. It is simple and easily administered in all clinical settings, including the emergency department, wards and out-patient clinics. This scale is composed of 15 items based on different parts of the neurological examination such as the level of consciousness, language, neglect, visual-field loss, extra-ocular movement, motor strength, ataxia, dysarthria, and sensory loss. The observer rates the patient’s ability to answer questions and perform activities so that each item is scored from 0 (normal) to a maximum of 2 to 4, according to the item tested. It takes less than 5 minutes to complete by trained people, and its reliability among health care providers is high. It is useful not only in evaluating the severity of stroke and in assessing the evolution of deficit over time, but also helps in the decision of treatment and in predicting patient outcome. This workshop aims at providing training skills in applying the NIHSS to patients with different neurological deficits due to stroke.

Special Issue on Stroke. From Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

arious stroke scales have been developed. They are useful to guide diagnostic accuracy, treatments, monitoring neurologic deficits and to predict outcomes.
The ABCD2 and, most recently, the ABCD3 or ABCD3-I score, have been developed to predict the stroke risk after transient ischaemic attack. They may also assist in selecting out non-cerebrovascular diagnoses if the score is low.
The Hunt and Hess scale describes the severity of subarachnoid haemorrhage based on the patient's clinical condition and is used as a predictor of outcome.
The TOAST classification is a system for categorization of subtypes of ischaemic stroke mainly based on etiology.
All these scales will be covered during the workshop.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Data from the literature concerning symptomatic carotid stenosis show that the long term benefits of surgery are greater when it is performed within 2 weeks after the event. The aim of this study is to evaluate our centre’s capacity and outcomes.
Methods: Forty-eight consecutive patients submitted to carotid endarterectomy (CEA) due to symptomatic carotid stenosis [3 ocular transient ischaemic attacks (TIA); 15 TIAs; 30 strokes] in a reference Vascular Surgery and Stroke centre were evaluated (July 2014 – June 2015). A prospective registry was made with follow-up from 6 months to a year. All the diagnoses were confirmed by a neurologist and a vascular surgeon. Patients with more than 180 days of waiting time for surgery were excluded (2 patients).

Results: The mean time from event to surgical proposal was 15 days (median 4) and from event to CEA was 28 days (median 10) (20 inpatients, 25 outpatients, 3 other hospitals). The median ABCD2 score after observation was 5. Ninety-two percent of the patients were operated under loco-regional anaesthesia, with 3 conversions to general anaesthesia (2 intra-operatory deficits after clamping with necessity of shunt, 1 intolerance). Most of the patients were submitted to patch closure (88%) and 8% with eversion. Post-operatively 6% of the patients needed reintervention due to neck hematoma, 1 had hyperperfusion syndrome and 1 had hypoperfusion syndrome. Thirty-day death/stroke rates were 0%, and at 1 year, 4 deaths were registered.

Conclusion: Fast-track protocols are needed for legis artis patient treatment. Primary referentiation also has to be optimized. Indications for surgery are well established and practiced. Surgery outcomes are according to the recommendations.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: While performing endovascular techniques for middle cerebral artery (MCA) recanalization in hyperacute stroke, there is some controversy regarding immediate stenting of a concomitant carotid stenosis, or postponing for endarterectomy in a more stable clinical condition within the first 2 weeks since symptom onset. Aiming to raise discussion around this issue, we present two acute stroke clinical cases where both attitudes could be considered.
Case Reports: Case 1: 57-year-old male, previously anticoagulated (rivaroxaban 20mg) for deep venous thrombosis, presented right MCA occlusion symptoms, scoring 15 on NIHSS. Angio-CT scan showed right ICA stenosis, and a thrombus in the right MCA M1 segment. Due to anticoagulation, the patient was immediately selected for thrombectomy (Thrombolysis in Cerebral Infarction (TICI) 2b), with an end-of-procedure NIHSS of 8. Duplex ultrasound confirmed a 75% ICA atherosclerotic stenosis. The patient was discharged to his reference hospital with indication for endarterectomy, scoring 3 on NIHSS. Case 2: 59-year-old female presented with left MCA occlusion symptoms, scoring 12 on NIHSS. Angio-CT showed occlusion of left ICA and MCA (M1 segment). We performed thrombolysis followed by MCA thrombectomy (TICI 3), with an end-of-procedure NIHSS score of 19; angiography showed a sub-obliterative ICA stenosis (>90%) at the end of the procedure (occlusion opened by the thrombectomy catheter passing through?), also observed in a duplex ultrasound exam. NIHSS subsequently improved to 4, and a successful endarterectomy was performed 7 days after admission.

Conclusion: Although we decided to postpone carotid stenosis treatment, using later endarterectomy instead of immediate endovascular treatment during the thrombectomy procedure, doubts were raised regarding the best approach. We suggest a systematic register of these cases in a multicentre study, to gather more information that might lead to supported decisions, as there are no current specific guidelines addressing this issue.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Nowadays, stroke centres use extensive imagological data to support hyperacute treatment of stroke. Although simple CT scan is enough to decide intravenous treatment, endovascular procedures obligate an angio-CT documenting an occlusion and some centres use perfusion CT to show a small core of infarct. Hyperacute treatment of symptomatic carotid stenosis is controversial, even more when referring to intracranial segments.
Case Report: A 57-year-old woman, with multiple cardiovascular risk factors, was admitted to our emergency department one day after an elective surgery. She clinically presented a right total anterior circulation infarction with 5 hours and 30 minutes of evolution (anosognosia, right conjugate eye deviation, left homonymous hemianopia, hemiparesis grade 3 and hemisensory loss), scoring 12 on NIHSS. The brain CT scan was normal. The CT angiogram showed a slight reduction in the diameter of the right carotid bulb and apparent severe stenosis of the cavernous segment of the internal carotid artery. CT perfusion revealed an elevated mean transit time with no apparent lesion on cerebral blood volume. First, we tried to improve perfusion with dopamine, but neurological deficits remained stable. After 1 hour and 30 minutes, we performed angioplasty with stenting of the cavernous segment of the internal carotid artery resulting in a frank improvement of symptoms. The final outcome revealed only a left hemiparesis (grade 4) with an NIHSS of 2.

Conclusion: Although controversial, acute endovascular treatment of intracranial symptomatic stenosis may be an option when best medical treatment is not feasible.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Sulcal effacement is widely regarded as an early CT sign of stroke. The authors present a case where the interpretation of this sign was confounded by other factors.

Clinical Case: A 45-year-old female patient, previously autonomous and without any relevant medical conditions, was admitted to the emergency room due to sudden onset of left hemiparesis, dysarthria and central facial paralysis. The patient was anosognosic and had a left-side sensory neglect (NIHSS 12). Brain CT revealed a right hyperdense middle cerebral artery sign, signs of early ischaemic changes on basal ganglia and fronto-insular cortex and sulcal effacement on the right fronto-parietal convexity, but preserving the cortical-subcortical differentiation. Intravenous thrombolysis was administered two hours after onset, and the patient was immediately transferred to a mechanical thrombectomy centre. On arrival the patient was stable. CT angiography confirmed the right M1 segment occlusion and the perfusion study was not readable due to motion artefacts. Mechanical thrombectomy was performed at four hours and forty-five minutes after onset, with complete recanalization of the affected territory (TICI 3). NIHSS at discharge was 5 (central facial paralysis and left hemiparesis). At one-month follow-up, she scored 2 on the NIHSS (mild left hemiparesis).

Discussion: This clinical case pretends to allude to the fact that sulcal effacement in an ischaemic onset might be due to cytotoxic oedema, but might also be due cerebral hyperaemia associated with compensatory vasodilation after an ischaemic insult, and thus falsely overestimate the ASPECTS score. Being so, the distinction is not only of major clinical relevance, but also influences the therapeutic approach.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Case Report: A 57-year old woman with multiple vascular risk factors and ulcerative colitis presented to our hospital after noticing speech impairment and headache when she woke up. This patient was taking, among other medications, acenocoumarol, methotrexate, prednisolone and adalimumab. Her initial ECG demonstrated atrial fibrillation and her CT scan showed acute haemorrhage of the right cerebellum. Anticoagulant therapy was stopped. The patient’s clinical status improved steadily during her stay at our centre. On the twenty third day, the haemorrhage had already been reabsorbed, and discussion was raised concerning the patient’s orientation. The haemorrhagic stroke was considered to be due to the patient’s history of hypertension. Despite the spontaneous haemorrhage, given the risk of further cardioembolic stroke episodes due to atrial fibrillation and associated risk factors, reinitiating anticoagulation was deemed necessary. At this stage, introducing a novel oral anticoagulant was considered. Nevertheless, this idea was discarded for the lack of experience regarding these drugs in ulcerative colitis patients on biologic drug therapy. This question was also debated with Cardiology and, to reduce haemorrhagic risk, left atrial appendage closure was considered and scheduled.

Conclusion: This patient illustrates the difficulties faced when dealing with multiple comorbidities and simultaneous risk of bleeding and ischaemia.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: The authors present a clinical case of an ischaemic stroke that presented with anomic aphasia.

Case Report: A 75-year old woman was brought to the emergency department with an anomic aphasia that had started that day. The neurological exam confirmed the anomic aphasia with no other associated findings. The CT-Scan showed focal points of ischaemic gliosis without any other acute changes that could suggest vascular lesions particularly in the middle cerebral artery territory. The patient was hospitalized in the cerebrovascular disease unit with the diagnosis of ischaemic stroke. During her stay at the unit, the patient developed a decreased nasolabial fold prominence on the left side, motor aphasia, dysmetria and a lack of balance while walking. On the fourth day, the patient underwent an MRI that revealed a sub-acute infarction in a partial territory of the left middle cerebral artery with a partially re-canalized thrombus in the inferior M2 branch of this artery. Blood work showed a mixed dyslipidaemia. The echocardiogram detected a type 1 diastolic dysfunction with an ejection fraction of 55%. Patient was discharged after 8 days. Currently, the patient is followed in the cerebrovascular diseases department. The neurological evaluation demonstrates aphasia with some impairment of comprehension and naming. Her speech has fluency loss showing occasional anomic pauses and paraphasia.

Conclusion: The authors alert to the fact that a stroke can present itself in multiple ways, stressing the role of the clinical symptoms in its diagnosis.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: The authors present a venous sinus thrombosis that started in a woman 10 days after labour.

Case Report: A 34-year old woman, who had gone into labour 10 days before her admission, presented to the emergency department with paraesthesia on the right side of the body and dysarthria which started that day. The neurological exam showed predominant right brachial paresis associated with a diminished sensitivity in the right arm and leg. The CT-Scan revealed a venous thrombosis that reached the straight, superior sagittal and transverse sinus, with a greater extension on the right side involving multiple tributary veins. The admission in the cerebral vascular diseases unit was followed by heparin perfusion. Ten days after the onset of the episode the patient was submitted to another CT-Scan that showed resolution of the thrombosis. Goldman campimetry was considered normal. The patient was discharged from the unit and started an etiologic search. The echocardiogram and cervical duplex ultrasound were normal. The blood work showed a positive lupus anticoagulant. Currently, the patient does not show any sequels and maintains anticoagulation.

Conclusion: The authors highlight the role of the internist in the diagnosis of a rare entity in a woman, 10 days after labour, without any relevant past medical history.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: First described by Jean Lhermitte, internuclear ophthalmoplegia is a disorder characterized by the inability of horizontal gaze conjugation with weakness in the adduction of the affected eye and horizontal nystagmus in abduction of the contralateral eye. This entity is commonly associated with a lacunar brainstem stroke, but also with multiple sclerosis, infection, trauma or tumour involving the medial longitudinal fascicles.

Case Report: A 71-year-old man went to the emergency department with binocular diplopia with 12 hours of evolution. He had personal antecedents of chronic hepatic disease, Child Pugh B, probably with alcoholic etiology. Upon physical examination, he was afebrile, normotensive, with limitation in adduction of the left eye and right eye nystagmus in conjugate gaze to the right, with no other changes. Analytically, he had thrombocytopenia of 57000/µL, the electrocardiogram showed no dysrhythmia and the CT was normal. The diagnosis of an ischaemic stroke of the posterior circulation was assumed, involving the medial longitudinal fasciculus. The patient was admitted for surveillance and stratification of cardiovascular risk. He experienced full recovery in 24 hours. Doppler ultrasound of the cervical and intracranial vessels showed severe focal stenosis of the left posterior cerebral artery and right and left carotid stenosis, estimated at 30 and 50%, respectively.

Conclusion: Internuclear ophthalmoplegia is a discreet and informative sign whose clinical recognition is essential for an accurate topographical diagnosis.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: In about 40% of younger patients with acute ischaemic stroke, the cause remains undefined despite an extensive diagnostic evaluation. Patent foramen ovale (PFO) is a hemodynamically insignificant interatrial communication present in about 25% of the adult population. Large PFO with a substantial shunt has been identified in many studies as an anatomical comorbidity associated with stroke.

Case report: We describe a case of a 49-year-old man who presented to the emergency department with left hemiplegia, left-sided neglect, and aphasia. Cranial computed tomography showed an acute left partial anterior circulation ischaemic stroke. Duplex ultrasound of the carotid arteries did not identify atherosclerotic lesions or reduced blood flow velocities. The patient had been healthy until this event, and his only apparent risk factor for vascular disease was smoking of approximately 15 cigarettes/day. Transoesophageal echocardiography was performed a week later and revealed a thromboembolus straddling a PFO. The patient was informed as to the options of treatment, and he decided to use long-term oral anticoagulation.

Conclusion: This case deals with a stroke cause that can be documented and treated both as primary and secondary prevention. The choices of antiplatelet agents, oral anticoagulants, transcatheter placement of an occlusive device or cardiac surgery present a broad range of options which entail different risks.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Mitral valve prolapse involves a spectrum of structural and functional mitral valve dysfunction, characterized by central weakening of the fibrous core tissue. Such lesions may lead to thrombus formation, vegetation and calcification of the valve that may cause thromboembolism. This condition may be asymptomatic, with stroke or transient ischaemic attack (TIA) being the first sign. Approximately 10-14% of ischaemic strokes occur in young adults. Studies revealed high incidence rates of hypertension, diabetes mellitus, dyslipidaemia and smoking as being the most frequent risks factors for ischaemic strokes.

Case Report: Male, 33 years, with hypertension and dyslipidaemia, medicated with ACE inhibitor and statin, with poor control. In April 1999, he went to the emergency room (ER) with the following complaints: right facial paraesthesia, dysarthria and headache with 24-hour duration. CT scan showed a small ischaemic lesion located in the left middle cerebral artery territory. Antiplatelet therapy was initiated with a successful and complete recovery. The TIA’s etiology was a mitral valve prolapse. Warfarin was initiated, as well as cardiology follow-up. Five years later, warfarin was discontinued and aspirin was resumed.

Conclusion: The patient was initially treated with aspirin at the ER but the cardiologist changed it to warfarin, which was discontinued in 2006 and changed back to aspirin. Since the duration of symptoms was 24 hours, the clinical distinction between TIA or stroke is difficult, with the constant revision of definitions contributing to that. This leads to different therapeutic approaches, as the guidelines support aspirin for cerebral transient ischaemic attacks and warfarin for selected post-stroke patients.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Stroke is a leading cause of death in our country. Although, there are better methods of detection and more effective treatments for prevention, their occurrence remains high. Thus, its prevention and proper treatment are crucial. In this sense, antiplatelet therapy (AT) gains an important role in primary and secondary prevention of events. However, the clinician cannot forget the side effects of this drug.

Case Report: Man, 81 years old. Personal background: breast neoplasm, hypertension, type 2 diabetes, lacunar stroke, anaemia (with constant need for transfusion support) due to intestinal angiodysplasia, aortic stenosis and coronary heart disease. Patient sought medical attention due to gastrointestinal bleeding. After a hospital stay, he returned home medicated with enoxaparin and indication for considering AT suspension. The attending physician opted to suspend clopidogrel and the patient presented an improvement of his haemoglobin.

Conclusion: This patient carries a high cardiovascular risk. Given the age of the patient and the fact that the risk of events seems to be more dependent on anaemia than the release of atherosclerotic plaques, wouldn’t it be more appropriate to suspend clopidogrel? The fact that the family denied invasive treatments seems to point to a knowledge of the unfavourable clinical situation, so controversial treatments should be avoided. Suspending AT can decrease the risk of bleeding and thus better control of anaemia, which reduces the risk of cardiovascular events. The quaternary prevention starts gaining ground in clinical practice and, in this case, it seems to have been the solution.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Despite the downward trend, stroke is a major cause of mortality and morbidity in Portugal and in the world, accounting for different degrees of disability, and consequently marked decrease in quality of life. Prevention, in its various levels, is the main strategy, stressing the importance of primary health care and family doctor's role.

Case report: 72-year-old male, widower, with controlled hypertension, type 2 diabetes mellitus, atrial fibrillation, dyslipidaemia and sleep apnoea. The patient had a history of multiple cerebral ischaemic events: acute ischaemic stroke in 2008 (right carotid artery), posterior circulation stroke with right carotid artery restenosis in 2014. In 2016, the patient underwent stenting of the basilar artery after episodes of vertebrobasiIar ischemia, under dual antiplatelet therapy and hypocoagulation. As a complication of enoxaparine use, he had a spontaneous rectus sheath hematoma. At the first consultation in primary care after discharge, the patient was clinically and analytically stable, but with a total loss of interest in all his daily activities. The medical focus was not only the risk factor control but the improvement of psychological and functional status.

Conclusion: Given the current population ageing, it becomes imperative to adjust the available health resources, in order to reduce the morbidity inherent to stroke. Tertiary prevention allows the patient reintegration, so that an interdisciplinary approach is fundamental. Post-stroke disability, especially the psychological impairment, constitute a major obstacle to the treatment adherence and rehabilitation. The knowledge of the patients' social and familiar context is key to treatment success.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Stroke in young patients has been receiving higher attention recently, mostly because global stroke incidence decreased in the last three decades. Nowadays, almost 10% of ischaemic strokes occur in patients younger than 50 years. The aim of this study is to report a case of stroke with internal carotid artery (ICA) dissection in a young patient and highlight the importance of rehabilitation.

Case report: A 41-year-old woman, with no relevant medical history, independent in the activities of daily living, was brought to the emergency room after being found lying on the floor unconscious, and having a history of throwing up and sudden headache with aura about 4 hours prior to the event. Physical examination revealed prostration (Glasgow Coma Scale of 13), right oculocephalic deviation, left hemianopsia, left central facial palsy, dysarthria and left hemiparesis. The CT scan showed a hypodensity compatible with acute ischaemic injury in the middle cerebral artery territory, or watershed regions. A CT angiography demonstrated occlusion of the right ICA with potential dissection. After 15 days of in-patient stay in the Stroke Unit, she was transferred to the Rehabilitation department to undergo an intensive rehabilitation program. She was admitted with a Functional Independence Measure (FIM) scale of 66/126, and left with 106/126.

Conclusion: Pathogenesis of stroke in young patients is challenging. Although rare, ICA dissection remains an important cause. Its diagnosis is usually difficult and so, the incidence may be underestimated. Rehabilitation treatment plays an important role in those patients, promoting patients’ independence, social/vocational reintegration and quality of life.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Pain after stroke is a very debilitating and underestimated condition, affecting patients’ quality of life. For its complex character, the main challenge is to recognize its prevalence and its developing process so as to enable an early approach and avoid its chronification.

Methods: A systematic review of the literature was completed using PubMed database, with 59 studies identified regarding the main causes of chronic pain after stroke, diagnostic strategies and therapeutic attitudes.

Results: A variety of direct and indirect processes can underlie pain after stroke. Previous musculoskeletal pathology that worsens due to neurological deficits, hemiplegic shoulder pain, pain related to spastic limbs and neuropathic pain (such as central pain and type I complex regional pain syndrome) are the main causes of post stroke chronic pain. Hemiplegic shoulder pain is the most common one and accounts for about 70-80% of them. Because of their own clinical and pathophysiological particularities, each is to be individually approached and treated.

Conclusion: Pain after stroke is not negligible. For its prevalence and impairment both in quality of life and rehabilitation process, it is essential to recognize the main causes as well as the diagnostic strategies and subsequent therapeutic alternatives.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Stroke has a large population impact not only for the high mortality, but also for its potential to generate motor and cognitive disability. Stroke patients have a 15–fold increased risk of a recurrence.

Case report: Female, 69 years old, went 3 times to the emergency room with dizziness and decreased strength and, on the fourth time, she had dysarthria and paresis of the right lower limb. The CT scan showed a cerebral infarction. She was discharged on the same day and medicated. Fifteen days after the onset of symptoms, she requested a consultation with her family doctor for medication renewal. On this consultation, she maintained dysarthria and paresis of the right leg. No referral for follow-up consultation and monitoring of the clinical status was found. During the consultation, the risk factors were identified and corrective measures were implemented. The investigation of the main causes of stroke showed no alterations on the echocardiogram and Holter monitoring. The carotid ultrasound revealed a 70-80% stenosis of the left internal carotid artery. The medication was reviewed and the patient was referred to a neurologist and to physical rehabilitation. Later on, she had an endarterectomy.

Conclusion: The follow-up of post-stroke patients should address the quantification of the disabilities and implement treatments. In order to reduce recurrent disabilities and mortality, identification and correction of the main risk factors, and a search for treatable causes of stroke, should be performed.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: There is a causal relationship between atrial fibrillation (AF) and stroke. Cardioembolic stroke accounts for 20-30% of ischaemic strokes and AF is the most common cause of cardioembolic stroke. This arrhythmia is relatively common in the general population and its prevalence increases with age.

Case Report: A 59-year-old male, with arterial hypertension (8 years of evolution), overweight (BMI = 29 kg/m2), without other cardiovascular risk factors, came for a routine hypertension visit, without any symptoms. Physical exam revealed irregular radial pulse on digital palpation, irregular rhythm on cardiac auscultation and blood pressure of 120/85mmHg. The remaining physical examination was normal. In a previous electrocardiogram (ECG), the rhythm was always sinus. An urgent ECG and thyroid function study were ordered. The patient came back in two days with ECG and levels of thyroid-stimulating hormone (TSH). At this consultation, the radial pulse and cardiac auscultation were regular in rhythm. TSH was 2.19 mU/L and ECG revealed sinus rhythm at a rate of 69 beats per minute and right bundle branch disturbance. An echocardiogram and 24-hour Holter monitoring were requested, whose results are pending.

Conclusion: The clinical case described aims to highlight the importance of heart rate measurement by pulse palpation and cardiac auscultation on routine consultations. This may identify possible arrhythmias in an opportunistic way. In this patient, further study should be pursued due to the possibility of paroxysmal arrhythmia.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Definition and prevalence: Hypertension has been defined (ESH/ESC guidelines 2013) as resistant (RH) to treatment when it is not controlled after a therapeutic strategy that includes adequate lifestyle measures plus a diuretic and two other anti-hypertensive drugs from different classes at adequate doses. Its prevalence is about 5-30% in hypertensive patients, and there is clear evidence that RH associates with abnormally high cardiovascular and renal morbidity and mortality. In Portugal, as shown by the Physa study, RH occurs in 8% of all treated hypertensive subjects with a prevalence of 5-10% in general practice and 25-30% in hypertension clinics. HR is more common in elderly people as well as in the obese, people with sleep apnoea, high salt intake, diabetes, renal disease, secondary hypertension, among others.
Strategy: Before RH is diagnosed, one must exclude resistance due to doctors and resistance due to patients. Resistance attributable to doctors includes: a) incorrect blood pressure (BP) measurements (non-adapted devices, cuffs, no BP evaluation in both arms and legs, Osler maneuverer…), b) inadequate regimens (incorrect combinations, low doses particularly of diuretics, furosemide given wrongly only once a day, inertia…), c) failure to identify white coat hypertension or white coat effect with 24h ambulatory BP monitoring (ABPM), d) no detection of drug interactions and potential pro-hypertensive drugs, e) failure to detect renal disease; f) failure to detect secondary hypertension (most prevalent forms are renal disease, primary hyperaldosteronism and sleep apnoea). Resistance due to patients includes: a) high salt intake (measurement of 24-h urinary sodium excretion is mandatory), high alcohol intake, low potassium intake, b) use of non-prescribed potential pro-hypertensive drugs; c) non-compliance to therapy (drug intake under surveillance and evaluation with ABPM is recommended). After all these items have been evaluated, further administration of mineralocorticoid receptor antagonists (e.g. spironolactone 12.5-25 mg/d) as a 4th drug has been shown to provide adequate BP control in a large percentage of suspected RH patients. If all these procedures fail to reverse or control RH, renal artery denervation or carotid sinus stimulation may be considered providing that there are no technical, anatomical or medical contraindications to these procedures.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

As the availability and quality of imaging techniques improve, doctors are identifying more patients with no history of transient ischaemic attack or stroke in whom imaging shows brain infarcts. Until recently, little was known about the relevance of these lesions.
Silent brain infarcts are common not only in selected patients but also in the general population of elderly people. They are far more common than stroke, both with respect to their prevalence and incidence. Cardiovascular risk factors known to increase the risk of stroke are also associated with silent brain infarcts, with hypertension being, by far, the strongest modifiable risk factor identified to date. Therefore, silent brain infarcts might differ from symptomatic infarcts only by the lack of acute stroke-like signs. However, they do present as subtle deficits in physical and cognitive function that commonly go unnoticed. Moreover, the presence of silent infarcts more than doubles the risk of subsequent stroke and dementia.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: New oral anticoagulants (NOACs) were shown, when compared to warfarin in a randomized controlled trial setting, to be effective in reducing the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients.

Objectives: This presentation will assess, with special emphasis on rivaroxaban, efficacy, safety and persistence/adherence in an “everyday clinical practice” population of drug-naïve NVAF patients treated with NOACs.

Methods: A PubMed® database non-systematic search of the latest articles published on efficacy, safety and persistence/adherence outcomes of NOACs as used in “everyday clinical practice” was performed.

Results: Efficacy, safety and persistence/adherence outcomes of NOACs in an “everyday clinical practice” population of drug-naïve patients with AF were consistent with the results of previous randomized controlled trials across a wide range of “real life” patients.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Once the time window for acute stroke revascularization treatments is narrow, a finely tuned stroke code strategy is mandatory to achieve good functional neurological results. In 2015, new trials on mechanical thrombectomy lead to new European recommendations (ESO, 2015) on acute stroke treatment, in addition to the already established intravenous thrombolytic treatment. While thrombolytic treatment can be provided in many hospitals that have computed tomography and a stroke team/unit, mechanical thrombectomy requires specialized neurointervention teams, which are available mostly in tertiary hospitals.
Aiming to provide thrombectomy treatment to a larger population, a metropolitan inter-hospital collaboration now allows a continuous availability of this treatment (24h/7d).
The pre-hospital emergency medical service delivers the suspected stroke patients (according to FAST – face, arm, speech, time) to the nearest hospital with a stroke team/unit in a 6-hour window after symptom onset. At these hospitals, thrombolysis may be administered, when indicated, within 4.5 hours of symptom duration.
Whenever a large artery occlusion is suspected, it is diagnosed with non-invasive imaging, whenever possible. If this is the case, and the patient is not recovering with intravenous thrombolysis or has contraindications for this treatment (e.g. anticoagulation), the on-call neuroradiologist is contacted and the patient is sent for endovascular treatment up to 6 hours after symptom onset.
Patients with unknown time of symptom duration are evaluated with multimodal imaging and treated accordingly. As the treatment time window for acute basilar artery occlusion is not well established, an individualized decision usually takes place, taking in consideration the clinical and imagiological potential for reversibility.
Most importantly, the decision to undertake mechanical thrombectomy is made jointly by a multidisciplinary team comprising, at least, a stroke physician and a neuroradiologist.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

The modified Rankin Scale (mRS) is a 7-level ordered categorical scale, which captures levels of patient functional independence following a stroke, with scores ranging from 0 (fully independent) to 6 (dead). The mRS has been reported to be a valid and reliable endpoint in randomized clinical trials and, as such, it is a common and recommended outcome measure in acute ischaemic stroke studies. In clinical practice, the mRS offers an easy and rapid assessment of the effect of a patient’s stroke on their activities and participation in a social context. Furthermore, its everyday use generally goes beyond stroke disability and broadens to global patient functional (in)dependence, aiding in several decisions concerning patient management. The application of a structured interview helps to classify patients in a more reliable way and improve inter-rater reliability.
Since the interpretation and application of this scale is so important to those who manage or conduct research on stroke, a focused workshop is provided, including pitfalls as well as practical use recommendations.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Introduction: Stroke is a common cause of morbidity and mortality. In fact, it is the leading cause of disability in the elderly. Spasticity occurs in up to 27% of patients in the acute phase of stroke and in up to 46% three months after the event.

The Central Nervous System (CNS) and intentional movements: The CNS is a coupling of increasingly complex systems regulated by themselves. Higher centres usually command lower centres, which, in turn, control the automatic and primitive behaviours, postural and tonic reflexes, associated reactions and balance.

Spasticity: Spasticity is an increase in tone (elastic hypertonia) that arises from pyramidal tract/upper motor neuron (UMN) injury, by the absence of its inhibitory action on the spinal reflexes and by a low threshold for myotatic activity. Lance (1980) put forward the most frequently accepted definition: spasticity is a motor disorder characterised by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex. Spasticity is not only velocity-dependent, but it is also length-dependent. For example, in the quadriceps, the tonic stretch reflex is greater when the muscle is short, than when it is long. It is indeed a component of the UMN syndrome (UMNS), but functional limitations after stroke are more closely related to overall neurological deficits, other than spasticity. The UMNS includes positive signs, such as spasticity, hyperreflexia, clonus, muscle spasms, Babinski reflex, synergistic movement patterns, antagonist-agonist co-contraction, spastic dystonia and associated reactions; and negative signs, such as muscle weakness, dexterity decrease and fatigability.
How does an UMN lesion cause spasticity? Each patient has injuries that affect different routes to varying extents, leading to adaptations in neural networks of the spinal cord. However, in all of them normal cortical-spinal tract functioning is absent. Different spinal mechanisms, such as membrane potential, reciprocal inhibition and presynaptic inhibition, may have different roles in different patients. Spasticity is likely to be caused not by a single mechanism, but by a complex chain of interrelated changes in different networks. Changing the balance between the above inhibitory spinal routes and excitatory pathways in the spinal cord, leading to a disinhibition of the stretch reflex. Spasticity appears only days to weeks after a central neurological injury. This delay between the acute lesion and the onset of spasticity is more than a phenomenon of mere disinhibition and suggests plastic changes in the CNS. An initial period of shock is followed by a transition period with the return of reflexes, not yet hyperactive. There appears to be a rearrangement, corresponding to neuronal plasticity in the spinal cord, and probably in the brain. Afferent fibres can grow and transform inhibitory and excitatory synapses. There is denervation hypersensitivity due to the upregulation of receptors. Furthermore, changes in the rheological properties and in the contractile soft tissue and musculoskeletal system (intrinsic hypertonia) are often associated with chronic spasticity and, in turn have been associated with increased spasticity.

Spasticity pattern of cerebral origin: This pattern observed after a stroke differs from spinal-origin spasticity as found in spinal cord injury and in multiple sclerosis. Cerebral-origin spasticity is characterized by a postural stereotype involving antigravity muscles: the upper limb presents a flexor pattern: depression of the scapula, internal rotation and adduction of the shoulder, forearm pronation, elbow, wrist and fingers flexion; the lower limb presents an extensor pattern: extension, adduction and internal rotation of the thigh, knee extension, plantar flexion and foot inversion. Spasticity is often classified according to the distribution of the affected body areas as focal, multifocal, regional or general. It is important to identify the distribution of spasticity since it has definite implications for treatment.

Rules of spasticity management: Spasticity does not always need to be treated. In fact, it may aid the patient to walk or perform other activities of daily living (ADL), maintain muscle mass and bone mineralization, and decreased oedema and the risk for deep vein thrombosis. However, it can interfere with mobility, exercise and range of motion, reducing the support and swing of gait and lead to contractures. It can also interfere with ADL and patient care, including hygiene. Moreover, pressure sores and sleep disturbance occur and can cause pain. In the treatment of spasticity, we may consider factors such as a chronical status, spasticity severity and distribution, location of the central lesion, patient comorbidities and caregiver availability. Treatment of spasticity should include three major classes of goals: technical (increasing the range of motion, reducing the tone or reducing spasm), functional (improving ADL, reducing pain, facilitating care, improving limb positioning and gait), and preventive (preventing contracture, skin maceration, and skin ulcers). Spasticity treatment should be performed by a multidisciplinary team that includes physiatrics, neurologists, nurses and caregivers, therapists, and should be always based on the person as a whole.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

There are a number of scoring systems used to determine an individual's risk of cardiovascular disease. Apart from giving an estimate of the risk of having a cardiovascular event or dying from a cardiovascular cause within, in general, ten years, they also indicate who is most likely to benefit from prevention. Therefore, these risk scoring systems are useful for the patient and for the clinician in deciding preventive medical treatment. The Framingham Risk Score, the first scoring system, estimates the cardiovascular risk of having an event at 10 years. Individuals with low risk have 10% or less coronary heart disease (CHD) risk at 10 years, with intermediate risk the value is 10-20%, and with high risk it is20% or more. The vast majority of younger adults are considered to be at “low risk” because of the weight of age and of the 10-year risk window, and thus the importance of addressing multiple moderate or single elevated risk factors for long-term CHD prevention. With these tools, we must recognize that age is the strongest predictor of cardiovascular risk. Almost all persons aged 70 and over are at >20% ten year cardiovascular risk and almost nobody aged under 40 is at >20% ten year cardiovascular risk. In the situation of young individuals with an extremely elevated risk factor, as is the case of cholesterol in familial hypercholesterolemia, the scoring system postpones treatment inadequately. Another problem with the majority of risk scoring systems is that they do not take into account factors like family history of cardiovascular disease, poverty and ethnicity. To measure the performance of a scoring risk system we should use: sensitivity/specificity/predictive value, discrimination, area under the Receiver Operating Characteristic (ROC) curve and the C statistic, calibration, positive and negative likelihood ratios and reclassification – the Net Reclassification Index (NRI) and the Integrated Discrimination Improvement (IDI).

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.

Deep venous thrombosis (DVT) is one of the most important, potentially preventable, causes of death and morbidity. Stroke confers a high risk of DVT (8-20%) in the absence of prophylactic treatment. Magnetic resonance studies show DVT in 40% of stroke patients, and in 18% of patients within 3 weeks of stroke. Colour Doppler ultrasound (CDU) reveals asymptomatic DVT in 18% of stroke patients.
Guidelines advise the routine assessments of risk of DVT on hospital admission for stroke, and initiation of prophylaxis especially in high-risk patients. Risk factors for DVT after stroke are the stroke severity, whenever imobility is present, as well as some comorbilities such as cardiac heart disease, cancer, increased body weigth index, and the presence of elevated D-dimers.
A review of 22 trials with low molecular weight heparin (LMWH) in ischemic stroke showed that, per 1000 patients, it can avoid 9 deaths, 3 pulmonary embolism (PE), 1 symptomatic DVT, although causing 6 major bleedings.
In intracranial hemorrhage (ICH), a meta-analysis of anticoagulant drugs for thromboprophylaxis that included 1000 ICH patients from 4 trials (2 randomized), revealed that the early use of enoxaparin or heparin (from 1 to 6 days after admission) could reduce PE (1.7% versus 2.9%), having a non-significant effect on mortality reduction (16.1% versus 20.9%), hematoma enlargement (8.0% versus 4.0%) or DVT (4.2% versus 3.3%).
Non-pharmacological measures aiming prophylaxis of venous thromboembolism (VTE) in stroke patients have been investigated in the last years. In CLOTS Trial 1, 2518 immobile stroke patients were allocated thigh-length graduated compression stockings or not, and, in CLOTS Trial 2, 3014 to thigh-length or below-knee graduated compression stockings. In both trials there were no statistically significant differences in VTE events and compression stockings increased the risk of skin breaks. Allocation to thigh-length graduated compression stockings was associated with a nonsignificant increased hazard of death in the first 6 months.
Intermittent pneumatic compression (IPC) has been developed to prevent DVT in stroke patients. A sequential compression allows increasing venous flow through the deep veins of the leg to reduce the likelihood of thrombosis, while it stimulates release of intrinsic fibrinolytic substances.
In a randomized trial of 151 ICH patients, IPC plus elastic stockings reduced asymptomatic DVT compared with elastic stockings alone (4.7% versus 15.9%).
CLOTS Trial 3 aimed to establish whether or not the routine application of IPC to the legs of immobile stroke patients, additionally to routine treatment, reduces their risk of DVT and PE. If providing robust estimates of the effectiveness of IPC in stroke patients, this could be extrapolated to other groups of medical patients at high risk of VTE. CLOTS Trial 3 primary outcome was DVT in the popliteal or femoral veins within 30 days of randomisation, either asymptomatic as detected on the first or second CDU performed as part of the trial protocol, or symptomatic DVT confirmed on imaging (either CDU or venography). The compression system used in this trial delivered a sequential circumferential compression and incorporated a venous refill technology so that the frequency of compression was tailored to the individual patient. The trial included 2876 acute stroke patients, 376 with ICH. Patients were allocated in a 1:1 basis to routine treatment or routine treatment plus IPC. The routine treatment included in each group 17% patients receiving prophylactic dose and about 14% patients receiving full-dose of anticoagulants. The IPC group had 3.6% less absolute risk of DVT (12.1% vs 8.5%), and a 34% risk reduction when adjusting for confounding factors. This effect was particularly prominent in ICH patients (6.7% versus 17.0% DVT cases). The Cox model showed a reduced probability for death up to 6 months after randomisation in those allocated IPC.
In secondary analyses from CLOTS 3, namely regarding cost-effectiveness of ICP, it was shown that IPC is inexpensive, prevents deep vein thrombosis, improves survival but not functional outcomes, and does not lead to a significant gain in quality-adjusted survival.
The current European Stroke Organization (ESO) recommendations to improve outcome and reduce the risk of DVT in immobile patients with intracranial hemorrhage are against short or long graduated compression stockings, and in favor of IPC; it is pointed that there is insufficient evidence from randomized controlled trials to make strong recommendations about how, when, and for whom anticoagulation should be given to prevent DVT or improve outcome.
Concerning ESO guidelines for prophylaxis of VTE in immobile patients with acute ischaemic stroke, it is also recommended that graduated compression stockings should not be used, while IPC (thigh-length, sequential) and prophylactic-dose anticoagulation can reduce the risk of VTE in those patients, the strongest evidence being for IPC. IPC should not be used in patients with open wounds on the legs and should be used with caution in those with existing DVT, heart failure, severe peripheral vascular disease or confusion where attempts to mobilise when unsupervised could lead to falls and injury. Prophylactic anticoagulation with unfractionated heparin (5000U, 2 or 3 daily), LMWH or heparinoid should be considered in patients whom the benefits of reducing the risk of VTE is high enough to offset the increased risks of intracranial and extracranial bleeding associated with their use.
ESO guidelines stat that further research is required to test whether neuromuscular electrical stimulation is effective. Additionally, it is highlighted that better methods are needed to define which stroke patients are at high enough risk of VTE acutely, or during later phases of care, to warrant prophylaxis, as well as to stratify their risk of bleeding on anticoagulants.

Special Issue on Stroke Update. From Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–9 June 2016.

Stroke is the leading cause of death in Portugal, greatly surpassing ischaemic heart disease. Largely ignored in the past, stroke has been the subject of intense research in the last decades, which led to the development of integrated care pathways with great impact on patients’ mortality and morbidity.
Raising awareness for acute and chronic management of stroke has been one of the focuses of the Cerebrovascular Diseases Study Group of the Faculty of Medicine of Porto and Hospital de São João. This group has regularly organised courses to discuss recent developments in stroke management and, in 2016, celebrates its 20th anniversary with the publication of this supplement. It also joyfully celebrates the first year the meeting bears the name of the recently created Porto University Centre of Medicine. This joint venture of the Faculty of Medicine of Porto and Hospital de São João will certainly help further our goals of fostering research, education and improved care in the area of stroke.
Mainly intended for General Practitioners, Internists, Neurologists and Physiatrists, the course also welcomes all healthcare professionals whose scope of care inevitably includes stroke patients. With a remarkably practical approach, it covers most aspects of the preventive and therapeutic management of cerebrovascular disorders.
In this supplement, you will find the abstracts from the lectures and also from the oral presentations of young physicians who elected to discuss their work during the course, and whose interest in the area of stroke we applaud.

Special Issue on Stroke. From the Porto University Center of Medicine Stroke Update Course, Porto, Portugal. 7–8 June 2016.